A role for lymphotoxin beta receptor in host defense against Mycobacteriumbovis BCG infection

To investigate the role of membrane lymphotoxin (LT)alpha 1/beta 2 and its LT beta receptor (LT beta R) in the protective immune response to Mycobacte rium bovis bacillus Calmette-Guerin (BCG) infection, we have used a soluble fusion molecule (LT beta R-IgG1). LT beta R-Ig treatment interferes with g ranuloma formation mainly in the spleen by inhibiting macrophage activation and nitric oxide synthase activity, in addition, a large accumulation of e osinophils was observed in the spleen of LT beta R-Ig-treated infected mice . Decreased blood levels of IFN-gamma and increased IL-4 were also observed , suggesting that the LT beta R pathway is important in BCG infection to fa vor a Th1 type of immune response. The treatment of transgenic mice express ing high blood levels of a soluble TNFR1-IgG3 fusion protein with LT beta R -Ig resulted in a still higher sensitivity to BCG infection, and extensive necrosis in the spleen. In conclusion, these results suggest that the LT be ta R and the TNFR pathways are not redundant in the course of BCG infection and protective granuloma formation: the LT beta R pathway appears to be im portant in spleen granuloma formation, whereas the TNFR pathway has a predo minant role in other tissues.